Open Access Research article

Maraviroc, a chemokine receptor-5 antagonist, fails to demonstrate efficacy in the treatment of patients with rheumatoid arthritis in a randomized, double-blind placebo-controlled trial

Dona L Fleishaker1*, Juan A Garcia Meijide2, Andriy Petrov3, Michael David Kohen4, Xin Wang1, Sujatha Menon1, Thomas C Stock1, Charles A Mebus1, James M Goodrich5, Howard B Mayer6 and Bernhardt G Zeiher7

Author affiliations

1 Pfizer Inc, 700 Chesterfield Parkway, St. Louis, MO, 63017, and Eastern Point Road, Groton, CT, 06340 USA

2 Hospital Ntra. Sra. de la Esperanza, 2 Santiago de Compostela, a Coruña15705,Spain

3 Crimean State Medical University, 69 Kyivska Street, Simferopol, 95017, Ukraine

4 Avivoclin Clinical Services, 5111 S Ridgewood Avenue, Suite 301, Port Orange, FL, 32127,USA

5 ViiV Healthcare, Five Moore Drive, Research Triangle Park, NC, 27709, USA

6 EMD Serono Inc., One Technology Place, Rockland, MA, 02370, USA

7 Astellas US LLC, Three Parkway North, Deerfield, IL, 60015, USA

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Citation and License

Arthritis Research & Therapy 2012, 14:R11  doi:10.1186/ar3685


See related editorial by Takeuchi and Kameda, http://arthritis-research.com/content/14/2/114

Published: 17 January 2012

Abstract

Introduction

The purpose of this study was to determine whether maraviroc, a human CC chemokine receptor 5 (CCR5) antagonist, is safe and effective in the treatment of active rheumatoid arthritis (RA) in patients on background methotrexate (MTX).

Methods

This phase IIa study comprised two distinct components: an open-label safety study of the pharmacokinetics (PK) of MTX in the presence of maraviroc, and a randomized, double-blind, placebo-controlled, proof-of-concept (POC) component. In the PK component, patients were randomized 1:1 to receive maraviroc 150 or 300 mg twice daily (BID) for four weeks. In the POC component, patients were randomized 2:1 to receive maraviroc 300 mg BID or placebo for 12 weeks. Patients were not eligible for inclusion in both components.

Results

Sixteen patients were treated in the safety/PK component. Maraviroc was well tolerated and there was no evidence of drug-drug interaction with MTX. One hundred ten patients were treated in the POC component. The study was terminated after the planned interim futility analysis due to lack of efficacy, at which time 59 patients (38 maraviroc; 21 placebo) had completed their week 12 visit. There was no significant difference in the number of ACR20 responders between the maraviroc (23.7%) and placebo (23.8%) groups (treatment difference -0.13%; 90% CI -20.45, 17.70; P = 0.504). The most common all-causality treatment-emergent adverse events in the maraviroc group were constipation (7.8%), nausea (5.2%), and fatigue (3.9%).

Conclusions

Maraviroc was generally well tolerated over 12 weeks; however, selective antagonism of CCR5 with maraviroc 300 mg BID failed to improve signs and symptoms in patients with active RA on background MTX.

Trial Registration

ClinicalTrials.gov: NCT00427934